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The expression of betatrophin (red) in the mouse liver increases cell division in pancreatic beta cells.
image by Peng Yi and Douglas Melton

A Helpful Hormone

by Nicole Kresge

Betatrophin increases the production of beta cells, the body’s insulin factories.

Insulin injections are a daily routine for many people with type 2 diabetes. The tide may be turning for them, however: HHMI Investigator Douglas Melton has found a hormone that dramatically increases the body’s store of insulin-producing beta cells in the pancreas.

For more than 10 years, Melton has focused on turning stem cells into beta cells as a potential treatment for diabetes. With more of these insulin producers in their bodies, diabetics may be able to forgo the insulin injections that help regulate blood sugar levels. When Melton heard about a synthetic molecule called S961 that inhibits insulin action, he wondered if mice given the molecule would compensate by producing more insulin, or even additional beta cells.

Peng Yi, a postdoctoral fellow in Melton’s Harvard University laboratory, injected mice with S961, and to his delight, the rodents started making more beta cells. But, as the researchers reported May 9, 2013, in Cell, when they tried adding S961 to beta cells in a dish, it had no effect, suggesting that it acts indirectly on beta cells. The missing link, they discovered, was a hormone the investigators named betatrophin.

Douglas Melton discusses the work that went into this discovery.

When the researchers turned on the betatrophin gene in the livers of mice, the number of beta cells in the animals’ pancreases tripled within 10 days and their blood sugar returned to normal levels. “It boosts beta cell replication more than anything anyone has ever observed,” says Melton. “It does it fast, and it does it specifically. The only cells in the body that divide [as a result of betatrophin activation] are the beta cells.” This makes betatrophin a promising potential therapy for people with type 2 diabetes.

Melton’s group is now working to find betatrophin’s receptor to figure out how it works. He also has partnered with companies Evotec and Janssen Pharmaceuticals to bring betatrophin to the clinic. “We’re counting on our partners to make [the hormone] in large amounts for testing in animals and then humans,” Melton says, adding that these first steps will take at least a year.